In a Video Game, Tackling the Complexities of Protein Folding

In a match that pitted video game players against the best known computer program designed for the task, the gamers outperformed the software in figuring out how 10 proteins fold into their three-dimensional configurations.

Proteins are essentially biological nano-machines that carry out myriad functions in the body, and biologists have long sought to understand how the long chains of amino acids that make up each protein fold into their specific configurations.

In May 2008, researchers at the University of Washington made a protein-folding video game called Foldit freely available via the Internet. The game, which was competitive and offered the puzzle-solving qualities of a game like Rubik’s Cube, quickly attracted a dedicated following of thousands of players.

The success of the Foldit players, the researchers report in this week’s issue of Nature, shows that nonscientists can collaborate to develop new strategies and algorithms that are distinct from traditional software solutions to the challenge of protein folding.

The researchers took pains to credit the volunteers who competed at Foldit in the last two years, listing “Foldit players” at the end of the report’s author list and noting that more than 57,000 players “contributed extensively through their feedback and gameplay.”

Zoran Popovic, a computer scientist at the University of Washington who was a lead author of the paper, said, “If things go according to plan, not too long from now, such massive author lists should be commonplace.” Foldit begins with a series of tutorials in which the player controls proteinlike structures on a computer display. In the game, as structures are modified, a score is calculated based on how well the protein is folded. Players are given a set of controls that let them do things like “shake,” “wiggle” and “rebuild” to reshape the backbone and the amino acid side shapes of a specific protein into a more efficient structure.

A list of top scores for each puzzle is posted so that players can compare their results. Players may also collaborate in teams, tracking progress on a separate list of group scores.

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The protein-folding problem can be solved by computers using statistical and related software algorithms, but it takes an immense amount of processing power.

“The problem is that these proteins are far, far more complex than a robotic arm, and can ‘fold’ in time frames measured in billionths of a second,” Duke Ferris, founder of the GameRevolution Web site, wrote recently. “It’s like trying to solve a million-sided Rubik’s Cube while it also spins at 10,000 r.p.m. And that’s for just one ‘fold.’ ”

In a comparison involving 10 separate protein-folding puzzles, video game players matched the results generated by software solutions in three of the puzzles, outperformed them in five cases and found significantly better solutions in two others, according to the scientists.

In addition to the acuity of human pattern-recognition skills, the researchers noted that players outperformed the best software tools in other ways as well, writing: “Humans use a much more varied range of exploration methods than computers. Different players use different move sequences, both according to the puzzle type and throughout the duration of a puzzle.”

The Foldit project was inspired by the volunteers who were contributing the downtime on their home computers to power a protein-folding program called Rosetta@home. The computer donors could see the progress of the program on their screens, and they began to note inefficiencies in the software’s folding approach. That led the scientists to look for ways to systematically harness the skills of the human volunteers.